SOKOLOVÁ, Jitka, B. JANOŠÍKOVÁ, JD TERWILLIGER, Tomáš FREIBERGER, JP KRAUS and Viktor KOŽICH. Cystathionine beta-synthase deficiency in Central Europe: Discrepancy between biochemical and molecular genetic screening for homocystinuric alleles. Human Mutation. 2001, vol. 18, No 6, 2 pp. ISSN 1059-7794.
Other formats:   BibTeX LaTeX RIS
Basic information
Original name Cystathionine beta-synthase deficiency in Central Europe: Discrepancy between biochemical and molecular genetic screening for homocystinuric alleles
Name in Czech Diskrepance mezi biochmeickým a molekulárně genetickým screeningem homocystinurických alel
Authors SOKOLOVÁ, Jitka (203 Czech Republic), B. JANOŠÍKOVÁ (203 Czech Republic), JD TERWILLIGER (840 United States of America), Tomáš FREIBERGER (203 Czech Republic, guarantor), JP KRAUS (840 United States of America) and Viktor KOŽICH (203 Czech Republic).
Edition Human Mutation, 2001, 1059-7794.
Other information
Original language English
Type of outcome Article in a journal
Field of Study Genetics and molecular biology
Country of publisher Czech Republic
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 6.134
RIV identification code RIV/00216224:14110/01:00036078
Organization unit Faculty of Medicine
Keywords in English homocystinuria; prevalence; mutation screening; cystathione beta-synthase; CBS; Czech; Slovak; ARMS-PCR
Tags ARMS-PCR, CBS, cystathione beta-synthase, Czech, homocystinuria, mutation screening, prevalence, Slovak
Changed by Changed by: prof. MUDr. Tomáš Freiberger, Ph.D., učo 24036. Changed: 27/6/2009 09:47.
Abstract
Recent reports suggested that homocystinuria due to cystathionine beta-synthase (CBS) deficiency is a more common inborn error of metabolism than originally thought. In this study we compared the prevalence of homocystinuric alleles ascertained by two different approaches. First, the incidence of homocystinuria estimated by selective biochemical screening in the Czech and Slovak Republics was 1:349,000 (95% CI 1:208,000-1:641,000). The two most common pathogenic mutant alleles found subsequently in these patients, IVS11-2A>C and c.833T>C, had a calculated population prevalence of 0.00042 (95% CI 0.00031-0.00055) and 0.00018 (95% CI 0.00013-0.00023), respectively. Second, to examine the possible negative detection bias of mildly affected patients we determined the prevalence of these two pathogenic mutations in a sample of 1284 unselected newborns. Indeed, the observed prevalence of the c.833T>C allele (0.00195, 95% CI 0.00063-0.00454) was 11x higher than in the previous group suggesting that many homozygotes for the c.833T>C had not been diagnosed by selective biochemical screening. The IVS11-2A>C allele was not detected among 2,568 newborn CBS alleles. The estimated incidence of homocystinuria of 1:83,000, calculated in a combined model, suggests that selective biochemical screening may ascertain only 25% of all homocystinuric patients. In conclusion, homocystinuria in Central Europe may be sufficiently common to consider sensitive newborn screening programs for this disease.
Abstract (in Czech)
V této studii byla porovnána prevalence alel spojených s homocystinurií dvěma přístupy. Incidence homocystinurie na základě výsledků biochemického screeningu je 1:349000. Dvě nejběžnější alely genu pro cystathionin beta-syntázu (IVS11-2A>C a c.833T>C)detekované u těchto pacientů, mají kalkulovanou populační frekvenci 0.00042, resp. 0,00018. Výskyt obou alel byl stanoven v souboru 1284 neselektovaných novorozenců (0.0, resp. 0.00195) a z kombinovaného modelu byla vypočtena frekvence onemocnění v české populaci 1:83000. To znamená, že biochemický screening zachytí pouze 25 % pacientů s homocystinurií.
PrintDisplayed: 25/4/2024 08:47